PROJECT SUMMAR/ABSTRACT The broad goal of the Bioinformatics Core is to support development of novel mouse models in The Jackson Laboratory (JAX) Center for Precision Genetics (JCPG) by developing and implementing the bioinformatics environment necessary for heterogeneous data integration and analysis, seamless data workflow among the Center components, and dissemination of data to the research community. In the JCPG model-generation pipeline, diverse data will be collected from patients and then analyzed using a suite of bioinformatics resources to identify the most appropriate variants for model generation. Precision genetic manipulation tools will then be used to construct the models, which will be developed in six disease areas in separate research projects. To support this model generation, the Bioinformatics Core will provide the integrative services to facilitate mapping between mouse and human variants, support network analysis for identification of potential gene interactions underlying the diseases modeled, implement processes for data storage and analysis, and design and implement tools that provide public access to data generated in each Center disease focus area. Specifically, the Core will: Aim 1) deploy analytical processes and standards, including comparative phenotype analysis, to support project workflows to prioritize candidate gene variants for animal models; Aim 2) enable refinement of candidate selection through polygenic and network-based analysis; Aim 3) employ digital methods and bioinformatics standards to track and document workflows and link this information to local and community informatics resources; and Aim 4) build and maintain a web site and data portal to provide free and open access to JCPG data. This Core will accomplish this by leveraging the powerful array of bioinformatics tools developed at JAX over many years and integrating them into a comprehensive system for variant discovery, model development and data dissemination. Specific existing tools to be used include GeneWeaver, a software tool for integrative data-driven discovery of the biological basis of disease, which will be used for selection of disease variants for model generation, data storage and analysis and implementation of the Center website and data portal. In addition, the Mouse Genome Informatics (MGI) resource, including, in particular the MGI Human Mouse Disease Connection resource, will support data integration, storage and dissemination. Together, the functions of the Bioinformatics Core will provide the robust and flexible bioinformatics system necessary for generation of precise mouse models of disease and free access to information about them.